This application claims priority under 35 U.S.C. xc2xa7119 of FR-98/14211, filed Nov. 12, 1998, hereby expressly incorporated by reference.
1. Technical Field of the Invention
The present invention relates to treating, for example soothing or calming, a variety of skin afflictions/conditions by administering to a candidate individual in need of such treatment an effective amount of at least one 2-amino-4-alkylaminopyrimidine 3-oxide compound.
2. Description of the Prior Art
It is known to this art that humans are subject to adverse cutaneous challenges or stimuli which are characterized by a sensation of skin discomfort, tautness, itchiness, a sensation of burning or warmth on the skin, or red blotches.
Active agents for controlling these types of conditions/afflictions have long been sought by researchers in this art.
Although various active agents have already been proposed, a constant interest remains to develop alternatives providing improved skin-soothing/calmant or anti-inflammatory activity, in particular for treating minor skin afflictions/conditions, such as, for example, sensitive skin, skin discomfort, tautness of the skin, itchiness of the skin, swelling of the skin, red blotchy skin or a sensation of burning or warmth on the skin.
Accordingly, a major object of the present invention is the provision of improved regime/regimen for treating and alleviating the symptoms of a variety of objectionable skin afflictions/conditions, while at the same time avoiding any appreciable side effects.
Briefly, the present invention features treating the aforesaid skin conditions/afflictions with a skin-soothing, -calmant or anti-inflammatory effective amount of at least one 2-amino-4-alkylaminopyrimidine 3-oxide compound formulated into a physiologically acceptable medium therefor.
More particularly according to the present invention, by the expression xe2x80x9cphysiologically acceptable mediumxe2x80x9d is intended a medium (e.g., vehicle, diluent or carrier) which is compatible with the skin, the mucous membranes, the nails and the hair of a human subject (hereinafter, simply the skin and/or the scalp).
The compounds of the 2-amino-4-alkylaminopyrimidine 3-oxide family which are well suited for administration according to the invention have the general formula (I): 
in which R1 is an alkyl radical having from 1 to 20 carbon atoms, and Z is a hydrogen atom or a radical xe2x80x94OR2, wherein R2 is an alkyl radical having from 1 to 12 carbon atoms, as well as the acyl derivatives and acid addition salts thereof.
According to the invention, by the expression xe2x80x9calkyl radicalxe2x80x9d is intended a linear or branched acyclic radical originating via the removal of a hydrogen atom from the molecule of a hydrocarbon, such as, for example, a methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl, hexadecyl, heptadecyl, octadecyl, nonadecyl or eicosadecyl radical.
In one preferred embodiment of the invention, R1 is an alkyl radical having from 6 to 12 carbon atoms, such as, for example, a hexyl, heptyl, octyl, nonyl, decyl, undecyl or dodecyl radical.
In another preferred embodiment of the invention, R2 is an alkyl radical having from 2 to 6 carbon atoms, such as, for example, an ethyl, propyl, butyl, pentyl or hexyl radical.
Preferred compounds according to the invention include:
2-amino-4-methylaminopyrimidine 3-oxide;
2-amino-4-ethylaminopyrimidine 3-oxide;
2-amino-4-propylaminopyrimidine 3-oxide;
2-amino-4-butylaminopyrimidine 3-oxide;
2-amino-4-pentylaminopyrimidine 3-oxide;
2-amino-4-hexylaminopyrimidine 3-oxide;
2-amino-4-heptylaminopyrimidine 3-oxide;
2-amino-4-octylaminopyrimidine 3-oxide;
2-amino-4-nonylaminopyrimidine 3-oxide;
2-amino-4-decylaminopyrimidine 3-oxide;
2-amino-4-undecylaminopyrimidine 3-oxide;
2-amino-4-dodecylaminopyrimidine 3-oxide;
2-amino-4-tridecylaminopyrimidine 3-oxide;
2-amino-4-tetradecylaminopyrimidine 3-oxide;
2-amino-4-pentadecylaminopyrimidine 3-oxide;
2-amino-4-hexadecylaminopyrimidine 3-oxide;
2-amino-4-heptadecylaminopyrimidine 3-oxide;
2-amino-4-octadecylaminopyrimidine 3-oxide;
2-amino-4-nonadecylaminopyrimidine 3-oxide;
2-amino-4-eicosadecylaminopyrimidine 3-oxide;
2-amino-4-methylamino-6-methoxypyrimidine 3-oxide;
2-amino-4-ethylamino-6-methoxypyrimidine 3-oxide;
2-amino-4-propylamino-6-methoxypyrimidine 3-oxide;
2-amino-4-butylamino-6-methoxypyrimidine 3-oxide;
2-amino-4-pentylamino-6-methoxypyrimidine 3-oxide;
2-amino-4-hexylamino-6-methoxypyrimidine 3-oxide;
2-amino-4-heptylamino-6-methoxypyrimidine 3-oxide;
2-amino-4-octylamino-6-methoxypyrimidine 3-oxide;
2-amino-4-nonylamino-6-methoxypyrimidine 3-oxide;
2-amino-4-decylamino-6-methoxypyrimidine 3-oxide;
2-amino-4-undecylamino-6-methoxypyrimidine 3-oxide;
2-amino-4-dodecylamino-6-methoxypyrimidine 3-oxide;
2-amino-4-tridecylamino-6-methoxypyrimidine 3-oxide;
2-amino-4-tetradecylamino-6-methoxypyrimidine 3-oxide;
2-amino-4-pentadecylamino-6-methoxypyrimidine 3-oxide;
2-amino-4-hexadecylamino-6-methoxypyrimidine 3-oxide;
2-amino-4-heptadecylamino-6-methoxypyrimidine 3-oxide;
2-amino-4-octadecylamino-6-methoxypyrimidine 3-oxide;
2-amino-4-nonadecylamino-6-methoxypyrimidine 3-oxide;
2-amino-4-eicosadecylamino-6-methoxypyrimidine 3-oxide;
2-amino-4-methylamino-6-ethoxypyrimidine 3-oxide;
2-amino-4-ethylamino-6-ethoxypyrimidine 3-oxide;
2-amino-4-propylamino-6-ethoxypyrimidine 3-oxide;
2-amino-4-butylamino-6-ethoxypyrimidine 3-oxide;
2-amino-4-pentylamino-6-ethoxypyrimidine 3-oxide;
2-amino-4-hexylamino-6-ethoxypyrimidine 3-oxide;
2-amino-4-heptylamino-6-ethoxypyrimidine 3-oxide;
2-amino-4-octylamino-6-ethoxypyrimidine 3-oxide;
2-amino-4-nonylamino-6-ethoxypyrimidine 3-oxide;
2-amino-4-decylamino-6-ethoxypyrimidine 3-oxide;
2-amino-4-undecylamino-6-ethoxypyrimidine 3-oxide;
2-amino-4-dodecylamino-6-ethoxypyrimidine 3-oxide;
2-amino-4-tridecylamino-6-ethoxypyrimidine 3-oxide;
2-amino-4-tetradecylamino-6-ethoxypyrimidine 3-oxide;
2-amino-4-pentadecylamino-6-ethoxypyrimidine 3-oxide;
2-amino-4-hexadecylamino-6-ethoxypyrimidine 3-oxide;
2-amino-4-heptadecylamino-6-ethoxypyrimidine 3-oxide;
2-amino-4-octadecylamino-6-ethoxypyrimidine 3-oxide;
2-amino-4-nonadecylamino-6-ethoxypyrimidine 3-oxide;
2-amino-4-eicosadecylamino-6-ethoxypyrimidine 3-oxide;
2-amino-4-methylamino-6-propyloxypyrimidine 3-oxide;
2-amino-4-ethylamino-6-propyloxypyrimidine 3-oxide;
2-amino-4-propylamino-6-propyloxypyrimidine 3-oxide;
2-amino-4-butylamino-6-propyloxypyrimidine 3-oxide;
2-amino-4-pentylamino-6-propyloxypyrimidine 3-oxide;
2-amino-4-hexylamino-6-propyloxypyrimidine 3-oxide;
2-amino-4-heptylamino-6-propyloxypyrimidine 3-oxide;
2-amino-4-octylamino-6-propyloxypyrimidine 3-oxide;
2-amino-4-nonylamino-6-propyloxypyrimidine 3-oxide;
2-amino-4-decylamino-6-propyloxypyrimidine 3-oxide;
2-amino-4-undecylamino-6-propyloxypyrimidine 3-oxide;
2-amino-4-dodecylamino-6-propyloxypyrimidine 3-oxide;
2-amino-4-tridecylamino-6-propyloxypyrimidine 3-oxide;
2-amino-4-tetradecylamino-6-propyloxypyrimidine 3-oxide;
2-amino-4-pentadecylamino-6-propyloxypyrimidine 3-oxide;
2-amino-4-hexadecylamino-6-propyloxypyrimidine 3-oxide;
2-amino-4-heptadecylamino-6-propyloxypyrimidine 3-oxide;
2-amino-4-octadecylamino-6-propyloxypyrimidine 3-oxide;
2-amino-4-nonadecylamino-6-propyloxypyrimidine 3-oxide;
2-amino-4-eicosadecylamino-6-propyloxypyrimidine 3-oxide;
2-amino-4-methylamino-6-butyloxypyrimidine 3-oxide;
2-amino-4-ethylamino-6-butyloxypyrimidine 3-oxide;
2-amino-4-propylamino-6-butyloxypyrimidine 3-oxide;
2-amino-4-butylamino-6-butyloxypyrimidine 3-oxide;
2-amino-4-pentylamino-6-butyloxypyrimidine 3-oxide;
2-amino-4-hexylamino-6-butyloxypyrimidine 3-oxide;
2-amino-4-heptylamino-6-butyloxypyrimidine 3-oxide;
2-amino-4-octylamino-6-butyloxypyrimidine 3-oxide;
2-amino-4-nonylamino-6-butyloxypyrimidine 3-oxide;
2-amino-4-decylamino-6-butyloxypyrimidine 3-oxide;
2-amino-4-undecylamino-6-butyloxypyrimidine 3-oxide;
2-amino-4-dodecylamino-6-butyloxypyrimidine 3-oxide;
2-amino-4-tridecylamino-6-butyloxypyrimidine 3-oxide;
2-amino-4-tetradecylamino-6-butyloxypyrimidine 3-oxide;
2-amino-4-pentadecylamino-6-butyloxypyrimidine 3-oxide;
2-amino-4-hexadecylamino-6-butyloxypyrimidine 3-oxide;
2-amino-4-heptadecylamino-6-butyloxypyrimidine 3-oxide;
2-amino-4-octadecylamino-6-butyloxypyrimidine 3-oxide;
2-amino-4-nonadecylamino-6-butyloxypyrimidine 3-oxide;
2-amino-4-eicosadecylamino-6-butyloxypyrimidine 3-oxide; and the branched isomers thereof.
More preferred compounds according to the invention include:
2-amino-4-hexylaminopyrimidine 3-oxide;
2-amino-4-octylaminopyrimidine 3-oxide;
2-amino-4-dodecylaminopyrimidine 3-oxide;
2-amino-4-octylamino-6-butyloxypyrimidine 3-oxide.
Even more preferred are 2-amino-4-dodecylaminopyrimidine 3-oxide, and 2-amino-4-octylamino-6-butyloxypyrimidine 3-oxide.
It will of course be appreciated that the subject 2-amino-4-alkylaminopyrimidine 3-oxide compounds can be administered either alone or in admixture.
In another embodiment of the invention compositions are formulated, in a physiologically acceptable medium therefor, comprising an effective amount of at least one 2-amino-4-alkylaminopyrimidine 3-oxide compound having the general formula (I), such compound or composition being well suited for controlling or alleviating the symptons of sensitive skin, skin disruptions, such as skin discomfort, tautness of the skin, itchiness of the skin, swelling of the skin, blotchy red skin or a sensation of burning or warming of the skin.
The compositions of the invention comprising at least one 2-amino-4-alkylaminopyrimidine 3-oxide compound are well suited for cosmetic applications.
The amount of the 2-amino-4-alkylaminopyrimidine 3-oxide compound required according to the invention of course depends on the desired effect and should be an amount which is effective for controlling the objectionable skin disruptions sought to be treated.
By way of example, the amount of compounds of the 2-amino-4-alkylaminopyrimidine 3-oxide family which are advantageously administered according to the invention typically ranges, for example, from 0.01% to 20% and preferably from 0.05% to 10% of the total weight of the composition.
The subject compositions are conveniently administered via any route, preferably via topical application onto the skin.
The physiologically acceptable medium (vehicle, diluent or carrier)into which the 2-amino-4-alkylaminopyrimidine 3-oxide compound is formulated according to the invention may be anhydrous or aqueous. By the expression xe2x80x9canhydrous mediumxe2x80x9d is intended a solvent medium containing less than 1% water. This medium is advantageously a solvent or mixture of solvents selected, in particular, from among C2-C4 lower alcohols, for example ethyl alcohol, alkylene glycols, for example propylene glycol, and alkylene glycol or dialkylene glycol alkyl ethers, in which the alkyl or alkylene radicals contain from 1 to 4 carbon atoms. By the expression xe2x80x9caqueous mediumxe2x80x9d is intended a medium advantageously of water or a mixture of water and another physiologically acceptable solvent, selected in particular from among the organic solvents indicated above. In the latter event, these other solvents, when they are indeed present, constitute about 5% to 95% by weight of the composition.
It is possible for the physiologically acceptable medium to contain other additives and adjuvants commonly formulated into cosmetics, such as surfactants, thickeners or gelling agents, cosmetic agents, preservatives or acidifying or basifying agents that are per se well known to this art, and in amounts which are sufficient to provide the desired physical state, in particular the form of a more or less thickened lotion, a gel, an emulsion or a cream. These can optionally be provided in a form pressurized as an aerosol or vaporized from a pump-dispenser bottle.
According to the invention, the subject compositions can comprise at least one compound of formula (I) with other active agents. Exemplary such other active agents include:
(a) other skin-soothing agents or calmants, for instance peptides such as, for example, the tripeptide lysine-proline-valine;
(b) keratolytic agents such as xcex1- and xcex2-hydroxycarboxylic acids or xcex2-ketocarboxylic acids, their salts, amides or esters and, more particularly, hydroxy acids such as glycolic acid, lactic acid, salicylic acid, citric acid and fruit acids in general, and 5-n-octanoylsalicylic acid;
(c) free-radical scavengers, such as xcex1-tocopherol or esters thereof, superoxide dismutases, certain metal-chelating agents or ascorbic acid and esters thereof;
(d) extracts of plant, marine or bacterial origin.
Other compounds can also be thus formulated, namely, for example, phospholipids such as lecithin, linoleic acid, linolenic acid, salicylic acid and the derivatives thereof described in FR-2,581,542, such as salicylic acid derivatives bearing an alkanoyl group substituent having from 2 to 12 carbon atoms in position 5 of the benzene ring, hydroxycarboxylic or ketocarboxylic acids and esters thereof, carotenoids, eicosatetraenoic acid and eicosatrienoic acid or the esters and amides thereof, and vitamin D and derivatives thereof.
The 2-amino-4-alkylaminopyrimidine 3-oxide compound, or cosmetic composition comprised thereof, is most conveniently topically applied onto those areas of the skin and/or the scalp of an individual requiring such treatment, optionally maintained in contact therewith for several hours and optionally rinsed therefrom.
Thus, the present invention also features a skin-soothing or calmant cosmetic regime/regimen for treating sensitive skin, skin disruptions such as skin discomfort, tautness of the skin, itchiness of the skin, swelling of the skin, blotchy red skin or a burning sensation or sensation of warmth on the skin, entailing topically applying a cosmetic composition comprising at least one 2-amino-4-alkylaminopyrimidine 3-oxide compound onto the skin and/or the scalp of an individual in need of such treatment, maintaining such composition in contact with the skin and/or the scalp for such period of time as required to elicit the desired therapeutic/anti-inflammatory effect, and optionally rinsing the composition therefrom.
Such cosmetic treatment permits enhancing the aesthetics and comfort of the skin and/or the scalp and enhancing an individual""s comfort by treating/alleviating the effects of adverse challenges on the skin.
In order to further illustrate the present invention and the advantages thereof, the following specific examples are given, it being understood that same are intended only as illustrative and in nowise limitative.